Low polydispersity poly-HEMA compositions

ABSTRACT

The present invention relates to compositions comprising poly-HEMA having a peak molecular weight between about 25,000 and about 100,000, preferably between 25,000 and 80,000 and a polydispersity of less than about 2 to less than about 3.8 respectively and covalently bonded thereon, at least one cross-linkable functional group. The present invention further relates to low polydispersity poly-HEMA suitable for making the crosslinkable prepolymers, processes for functionalizing and purifying said poly-HEMA to form said crosslinkable prepolymers, viscous solutions made from said crosslinkable prepolymers, hydrogels made from said viscous solutions and articles made from said crosslinkable polymers, hydrogels and viscous solutions.

RELATED APPLICATION INFORMATION

[0001] This patent application claims priority of a provisionalapplication, U.S. Ser. No. 60/363,639 which was filed on Mar. 11, 2002.

FIELD OF THE INVENTION

[0002] This invention relates to poly-HEMA compositions having aspecific molecular weight range and polydispersity. Methods for makingcontact lenses from said poly-HEMA and the contact lenses made thereofare also disclosed.

BACKGROUND OF THE INVENTION

[0003] Contact lenses have been used commercially to improve visionsince the 1950s. Most current contact lenses are made of hydrogelsformed by polymerizing hydrophilic monomers such as HEMA andvinylpyrrolidone in the presence of a minor amount of a crosslinkingagent. The polymerization of the monomers results in shrinkage which maybe as much as 20% by volume.

[0004] Prepolymers having backbones of PVA and reactive groups ofacrylic groups have been disclosed. The reactive prepolymer is dissolvedin water, and crosslinked inside a mold by irradiation with UV light toform a contact lens. The shrinkage during cure is small, but thehydrogels thus produced exhibits mechanical properties that may provemarginal for contact lens use.

[0005] U.S. Pat. Nos. 4,495,313, 4,889,664 and 5,039,459 disclose theformation of conventional hydrogels.

DESCRIPTION OF THE FIGURE

[0006]FIG. 1 shows Hansen Solubility Parameter spheres for thecompositions made in the Examples.

DESCRIPTION OF THE INVENTION

[0007] The present invention relates to compositions comprisingpoly-HEMA having a peak molecular weight between about 25,000 and about100,000, preferably between 25,000 and 80,000 and a polydispersity ofless than about 2 to less than about 3.8 respectively and covalentlybonded thereon, at least one cross-linkable functional group.

[0008] The present invention further relates to low polydispersitypoly-HEMA suitable for making the crosslinkable prepolymers of thepresent invention, processes for functionalizing and purifying saidpoly-HEMA to form said crosslinkable prepolymers, viscous solutions madefrom said crosslinkable prepolymers, hydrogels made from said viscoussolutions and articles made from said crosslinkable polymers, hydrogelsand viscous solutions. Still further, the present invention relates toprocesses for making said viscous solutions, hydrogels and articles.Preferred articles include medical devices, and specifically contactlenses.

[0009] We have discovered that the undesirable shrinkage, expansion andrelated problems possessed by poly-HEMA hydrogels may be overcome byproducing hydrogels from a crosslinkable prepolymer having a relativelylow molecular weight and low polydispersity. We have also discoveredthat poly-HEMA having a relatively low molecular weight and lowpolydispersity can be prepared by new practical methods and have usefulapplications in themselves. In addition, the poly-HEMA of the presentinvention can be converted into crosslinkable prepolymers useful formaking a number of articles, including hydrophilic coatings and contactlenses with improved mechanical properties. Finally the crosslinkableprepolymers of the present invention permit the production of highprecision molded articles.

[0010] As used herein “poly-HEMA” means polymers which comprise2-hydroxethyl methacrylate repeat units. The poly-HEMA of the presentinvention has a peak molecular weight in the range from about 25,000with a polydispersity of less than about 2 to a peak molecular weight ofabout 100,000 with a polydispersity of less than about 3.8. Preferably,the compositions of the present invention have a peak molecular weightbetween about 30,000 with a polydispersity of less than about 2 andabout 90,000 with a polydispersity of less than about 3.5. Morepreferably, the compositions of the present invention have a peakmolecular weight between about 30,000 with a polydispersity of less thanabout 2 and about 80,000 with a polydispersity of less than about 3.2.Suitable poly-HEMA may also have a peak molecular weight below about100,000 and a polydispersity of less than about 2, and preferably a peakmolecular weight between about 45,000 and 100,000 and a polydispersityof less than about 2.5. In certain embodiments the polydispersity isless than about 2.5, preferably less than about 2, more preferably lessthan about 1.7 and in some embodiments is less than about 1.5. The termpoly-HEMA as used above and throughout this specification will includepolymers prepared from 2-hydroxethyl methacrylate alone as well ascopolymers with other monomers or co-reactants as further describedbelow.

[0011] The poly-HEMA of the present invention should be substantiallyfree from branched polymer chains and gel particles. Gel particles areinsoluble pieces of polymer believed to be polymer chains crosslinked bydi- or multifunctional monomers. By “substantially free from” we meanless than about 0.1 weight % gel particles and/or branched polymerchains. Low crosslinker concentration in the HEMA monomer is thereforerequired. Preferably the amount of crosslinker is less than about 1%,more preferably less than about 0.5% and in some embodiments less thanabout 0.25% based upon all components present. All weight % are basedupon all components present unless otherwise specified. Crosslinkers arecompounds with two or more polymerizable functional groups. Examples ofcrosslinkers include TEGDMA (tetraethyleneglycol dimethacrylate),TrEGDMA (triethyleneglycol dimethacrylate), trimethylolpropanetrimethacrylate (TMPTMA) and ethyleneglycol dimethacylate (EGDMA). EGDMAis frequently present in the commercial 2-hydroxyethyl methacrylatemonomer which is used to make the poly-HEMA of the present invention.Care must therefore be taken to purchase HEMA monomer which has lowEGDMA concentration as defined herein. Suitable grades of HEMA monomermay be purchased from Röhm GmbH Chemische Fabrik D-64 293 DarmstadtGermany.

[0012] Suitable comonomers which may be polymerized with the HEMAmonomer include hydrophilic monomers such as vinyl-containing monomersand hydrophobic monomers as well as tinted monomers giving lightabsorption at different wavelengths. The term “vinyl-type” or“vinyl-containing” monomers refer to monomers comprising the vinyl group(—CR=CR′R″, in which R, R′ and R″ are monovalent substituents), whichare known to polymerize relatively easily. Suitable vinyl-containingmonomers include N,N-dimethyl acrylamide (DMA), glycerol methacrylate(GMA), 2-hydroxyethyl methacrylamide, polyethyleneglycolmonomethacrylate, methacrylic acid (MAA), acrylic acid, N-vinyl lactams(e.g. N-vinyl-pyrrolidone, or NVP), N-vinyl-N-methyl acetamide,N-vinyl-N-ethyl acetamide, N-vinyl-N-ethyl formamide, N-vinyl formamide,vinyl carbonate monomers, vinyl carbamate monomers, oxazolone monomersmixtures thereof and the like.

[0013] Still further examples are the hydrophilic vinyl carbonate orvinyl carbamate monomers disclosed in U.S. Pat. Nos. 5,070,215,4,711,943 and the hydrophilic oxazolone monomers disclosed in U.S. Pat.No. 4,910,277, the disclosures of which are incorporated herein byreference. Other suitable hydrophilic monomers will be apparent to oneskilled in the art.

[0014] More preferred hydrophilic monomers which may be incorporatedinto the polymer of the present invention include hydrophilic monomerssuch as DMA, GMA, 2-hydroxyethyl methacrylamide, NVP, polyethyleneglycolmonomethacrylate, MAA, acrylic acid and mixtures thereof. DMA, GMA andMAA are the most preferred in certain embodiments.

[0015] It is important that the selected hydrophobic monomers arepolymerized with the HEMA in a concentration and using methods whichresult in adequate solubility of the resulting poly-HEMA in the selecteddiluent and which also do not hinder the reactivity of the hydroxylgroups on the poly-HEMA or the reactivity of the crosslinkablefunctional groups on the crosslinkable prepolymer.

[0016] Suitable hydrophobic monomers include silicone-containingmonomers and macromers having a polymerizable vinyl group. Preferablythe vinyl group is a methacryloxy group. Examples of suitable siliconecontaining monomers and macromers include mPDMS type monomers, whichcomprise at least two [—Si—O—] repeating units, SiGMA type monomerswhich comprise a polymerizable group having an average molecular weightof about less than 2000 Daltons, a hydroxyl group and at least one“—Si—O—Si—” group and TRIS type monomers which comprise at least oneSi(OSi—)₃ group. Examples of suitable TRIS monomers includemethacryloxypropyltris(trimethylsiloxy)silane,methacryloxypropylbis(trimethylsiloxy)methylsilane,methacryloxypropylpentamethyldisiloxane, mixtures thereof and the like.

[0017] Preferably, the mPDMS type monomers comprise total Si andattached O in an amount greater than 20 weight percent, and morepreferably greater than 30 weight percent of the total molecular weightof the silicone-containing monomer. Suitable mPDMS

[0018] monomers have the formula.

[0019] Examples of suitable linear mono-alkyl terminatedpolydimethylsiloxanes (“mPDMS”) include:

[0020] where b=0 to 100, where it is understood that b is a distributionhaving a mode approximately equal to a stated value, preferably 4 to 16,more preferably 8 to 10; R₅₈ comprises a polymerizable monovalent groupcontaining at least one ethylenically unsaturated moiety, preferably amonovalent group containing a styryl, vinyl, (meth)acrylamide or(meth)acrylate moiety, more preferably a methacrylate moiety; each R₅₉is independently a monovalent alkyl, or aryl group, which may be furthersubstituted with alcohol, amine, ketone, carboxylic acid or ethergroups, preferably unsubstituted monovalent alkyl or aryl groups, morepreferably methyl; R₆₀ is a monovalent alkyl, or aryl group, which maybe further substituted with alcohol, amine, ketone, carboxylic acid orether groups, preferably unsubstituted monovalent alkyl or aryl groups,preferably a C₁₋₁₀ aliphatic or aromatic group which may include heteroatoms, more preferably C₃₋₈ alkyl groups, most preferably butyl; and R₆₁is independently alkyl or aromatic, preferably ethyl, methyl, benzyl,phenyl, or a monovalent siloxane chain comprising from 1 to 100repeating Si—O units.

[0021] The mPDMS type monomers are disclosed more completely in U.S.Pat. No. 5,998,498, which is incorporated herein by reference.

[0022] Preferably in the SiGMA type monomer silicon and its attachedoxygen comprise about 10 weight percent of said monomer, more preferablymore than about 20 weight percent. Examples of SiGMA type monomersinclude monomers of Formula I

[0023] Wherein the substituents are as defined in U.S. Pat. No.5,998,498, which is incorporated herein by reference.

[0024] Specific examples of suitable SiGMA type monomers include2-propenoic acid,2-methyl-2-hydroxy-3-[3-[1,3,3,3-tetramethyl-1-[trimethylsilyl)oxy]disiloxanyl]propoxy]propylester

[0025] and(3-methacryloxy-2-hydroxypropyloxy)propyltris(trimethylsiloxy)silane.

[0026] Additional suitable hydroxyl-functionalized silicone containingmonomers are disclosed in U.S. Pat. Nos. 4,235,985 4,139,513 and4,139,692 which are hereby incorporated by reference.

[0027] Yet further examples of SiGMA type monomers include, withoutlimitation (3-methacryloxy-2-hydroxypropyloxy)propylbis(trimethylsiloxy)methylsilane.

[0028] It is essential that the ratio between hydrophilic andhydrophobic monomers is such that a functionalized crosslinkableprepolymer prepared from the poly-HEMA can be dissolved and cured in thehydrophilic diluents described below.

[0029] Also hydrophobic monomers like methylmethacrylate andethylmethacrylate may be incorporated into the poly-HEMA to modify thewater absorption, oxygen permeability, or other physical properties asdemanded by the intended use. The amount of comonomer is generally lessthan about 50 weight %, and preferably between about 0.5 and 40 weight%. More specific ranges will depend upon the desired water content forthe resulting hydrogel, the solubility of the monomers selected anddiluent selected. For example, when the comonomer comprises MMA, it maybe beneficially included in amounts less than about 5 weight % andpreferably between about 0.5 and about 5 weight %. In another embodimentthe comonomer comprises GMA in amounts between up to about 50 weight %,preferably between about 25 and about 45 weight %. In yet anotherembodiment the comonomer comprises DMA in amounts up to about 50 weight%, and preferably in amounts between about 10 and about 40 weight %.

[0030] Initiators and chain transfer agents may also be used. Anydesirable initiators may be used including, without limitation,thermally activated initiators, UV and/or visible light photoinitiatorsand the like and combinations thereof. Suitable thermally activatedinitiators include lauryl peroxide, benzoyl peroxide, isopropylpercarbonate, azobisisobutyronitrile, 2,2-azobisisobutyronitrile,2,2-azobis-2-methylbutyronitrile and the like. Preferred initiatorscomprise 2,2-azobis-2-methylbutyronitrile (AMBM) and/or2,2-azobisisobutyronitrile (AIBN).

[0031] The initiator is used in the reaction mixture in effectiveamounts, e.g., from about 0.1 to about 5 weight percent, and preferablyfrom about 0.1 to about 2 parts by weight per 100 parts of reactivemonomer.

[0032] The poly-HEMA of the present invention may be formed in a numberof ways. In one embodiment HEMA monomer and any desired comonomers arepolymerized via free radical polymerization. The polymerization isconducted in any solvent, which is capable of dissolving the HEMAmonomer and the resulting poly-HEMA during the polymerization. Suitablesolvents for the polymerization of the HEMA monomer include alcohols,glycols, polyols, aromatic hydrocarbons, ethers, esters, ester alcohols,ketones, sulfoxides, pyrrolidones, amides mixtures thereof and the like.Specific solvents include methanol, ethanol, isopropanol, 1-propanol,methyllactate, ethyllactate, isopropyllactate, glycolethers like theDowanol range of products, ethoxypropanol, DMF, DMSO, NMP,cyclohexanone, mixtures thereof and the like. Preferred solvents includealcohols having one to four carbon atoms and more preferably, ethanol,methanol and isopropanol. Sufficient solvent must be used to dissolvethe monomers. Generally about 5 to about 25 weight % monomers in thesolvent is suitable.

[0033] The free radical polymerization is conducted at temperaturesbetween about 40° and about 150° C. The upper limit will be determinedby the pressure limitation of the equipment available and the ability tohandle the polymerization exotherm. The lower limit will be determinedby the maximum acceptable reaction time and/or properties of initiator.For polymerization at about ambient pressure a preferred temperaturerange is between about 50° C. and about 110° C., and more preferablybetween about 60° to about 90° C. and for times necessary to provide thedesired degree of conversion. A free radical polymerization reactionproceeds relatively fast. Between about 90 to about 98% of the monomerreacts within about one to about 6 hours. If a more complete conversionis desired, (greater than about 99%), the reaction may be conducted fromabout 12 to about 30 hours, and more preferably between about 16 andabout 30 hours. Since the poly-HEMA prepared in the polymerization stepin many instances will undergo a fractionation to remove low molecularweight species, it may not, in all embodiments, be required to bring thepolymerization process to a high degree of conversion. Pressure is notcritical and ambient pressures may be conveniently used.

[0034] Chain transfer agents may optionally be included. Chain transferagents useful in forming the poly-HEMA used in the invention have chaintransfer constants values of greater than about 0.001, preferablygreater than about 0.2, and more preferably greater than about 0.5.Suitable such chain transfer agents are known and include, withoutlimitation, aliphatic thiols of the formula R−SH wherein R is a C₁ toC₁₂ aliphatic, a benzyl, a cycloaliphatic or CH₃(CH₂)_(x)—SH wherein xis 1 to 24, benzene, n-butyl chloride, t-butyl chloride, n-butylbromide, 2-mercapto ethanol, 1-dodecyl mercaptan, 2-chlorobutane,acetone, acetic acid, chloroform, butyl amine, triethylamine, di-n-butylsulfide and disulfide, carbon tetrachloride and bromide, and the like,and combinations thereof. Generally, about 0 to about 7 weight percentbased on the total weight of the monomer formulation will be used.Preferably dodecanethiol, decanethiol, octanethiol, mercaptoethanol, orcombinations thereof is used as the chain transfer agent.

[0035] In some embodiments it is preferred to polymerize the poly-HEMAwithout a chain transfer agent. In this case alcohols are used as thesolvent, preferably alcohols having one to four carbon atoms, andpreferably the solvent is methanol, ethanol, isopropanol and mixturesthereof.

[0036] The poly-HEMA formed in the free radical polymerization has apolydispersity which is too high for direct use in the presentinvention. This is caused by the reaction kinetics of the process inwhich an important terminating reaction is a combination of two growingpolymer chains. Accordingly, when using free radical polymerization toform the poly-HEMA of the present invention it is necessary to purifythe poly-HEMA either before or after functionalization to remove thepolymer having molecular weights outside the desired range. Any methodcapable of separating a material based upon molecular weight may beused.

[0037] Fractionation using solvent/non-solvents may be used.Purification of HEMA copolymers via precipitation via the drop-wiseaddition of a HEMA copolymer to a non-solvent has been described in U.S.Pat. No. 4,963,159. The precipitated HEMA copolymer may then bedissolved in a solvent to obtain a solution that is substantially freefrom unpolymerized monomer.

[0038] The solvent and non-solvent may be selected on the bases ofHansen Solubility parameters to remove undesirably high molecular weightpoly-HEMA to form the poly-HEMA of the present invention. HansenSolubility Parameters describe polymer-liquid interactions and eachsolvent and polymer can be assigned a set of three parameters δ_(H),δ_(P), δ_(D), describing their interactions. A description of the systemis found in Handbook of Polymer Liquid Interaction Parameters andSolubility Parameter, CRC Press, Inc. 1990 and Handbook of SolubilityParameters and Other Cohesion Parameters, A. F. M. Barton, CRC Press,1985, Table 5. Each set of three parameters defines a point in athree-dimensional solubility space.

[0039] For a liquid to act as a solvent for a polymer, the parameters ofthe solvent must be close to those of the polymer. The Hansen solubilityparameters of a poly-HEMA can be determined by solubility tests in whicha sample of the polymer is stored in a number of different solvents. Byobserving whether the polymer is dissolved, swelled or unchanged, it ispossible to plot a solubility sphere for the particular poly-HEMA in thesolubility space substantially as described in Hansen SolubilityParameters; A User's Handbook, Charles M. Hansen, pg 43-53, CRC Press2000 and CMH's Sphere computer program for the calculations. Parametersfor some poly-HEMA compositions are listed in Table 1, below and plottedin FIG. 1. TABLE 1 MW (kDaltons) D P H R 75 16.9 18.1 20.1 8.3 55 17.216 17 10.4 35 18 15.2 15.4 11.7 23 17 14.2 13.6 13.2 14 17 14.2 13.613.2 2 18 14 13.2 13.7 1.3 18 14 13.2 13.7

[0040] For fractionation the poly-HEMA is dissolved in a solvent that isinside the solubility sphere for the polymer. Suitable solvents havesolubility parameters in the following ranges: δ_(D) from about 13 toabout 20, δ_(p) from about 5 to about 18, and δ_(H) from about 10 toabout 25. More preferred the distance between the solvent and thepolymer in the three-dimensional solubility space should not exceed thefollowing values: δ_(D) from about 5 to about 10, δ_(P) from about 4 toabout 12, δ_(H) from about 10 to about 6.

[0041] Once the poly-HEMA is dissolved, a non-solvent that decreases(moves toward the origin) at least one of the solubility parameters ofthe resultant separation mixture is gradually added to the dissolvedpoly-HEMA solution until the desired degree of precipitation of highmolecular weight material is obtained. It is not necessary to reduce allthree solubility parameters. In many embodiments it will be sufficientto reduce only one of the parameters such as the δ_(H) parameter. Inother embodiments it will be advantageous to reduce both the δ_(H) andthe δ_(P) parameters. We have found that often a surprising smallreduction (as little as about 2 to about 5 units) of the solventparameters will give the desired separation.

[0042] The non-solvent must reduce at least one of the parameters toinsure the selective precipitation of the poly-HEMA having a peakmolecular weight of greater than about 90,000. If the non-solventincreases the solubility parameters of the separation mixture,precipitation is much less a function of the molecular weight, andpoly-HEMA within the desired molecular weight range is lost.

[0043] When adding the non-solvent to the polymer solution it can bedifficult to avoid localized high concentration of the non-solvent. Thiswill result in a local unspecific precipitation of polymer. In suchcases it will be useful to stop the addition until equilibrium is againestablished. Non-specific precipitation may also be minimized byincreasing the temperature of the separation mixture until the mixtureis clear or adding the non-solvent at a somewhat higher temperature andthen lowering the temperature until the desired separation is obtained.The separation may be aided by known means such as, but not limited to,centrifugation.

[0044] The amount and rate of precipitation will vary depending upon thetemperature at which the separation is conducted, the solubilityparameters of the non-solvent and rate at which the non-solvent is addedand whether there is adequate mixing of the non-solvent. Depending onthe molecular weight of the poly-HEMA produced by the free radicalpolymerisation the amount of polymer precipitated may be between about 5and about 50% of the total poly-HEMA in the solution to obtain thedesired removal of high molecular weight polymer.

[0045] The high molecular weight poly-HEMA precipitates from thesolvent/non-solvent mixture and may be separated by conventional meanssuch as filtration, centrifugation and the like. If further separationis desired the fractionation can be repeated by further lowering of thesolvent parameters as described above. Again it will primarily be thematerial with the highest molecular weight that separates out and can beremoved from the solution.

[0046] The high molecular weight poly-HEMA, which is desirablyselectively removed, has a high viscosity in solution. This can in someinstances give a very difficult separation when using the methoddescribed above. The present invention therefore provides an alternatefractionation method wherein a homogeneous solution of poly-HEMA iscooled slightly so the polymer solution separates into two liquid phasesaccording to molecular weight range. The method comprises the followingsteps:

[0047] 1. Prepare a solution of poly-HEMA in a solvent using the Hansensolubility ranges and within the ranges defined above.

[0048] 2. Determine the separation temperature, T_(s), of the solutionby cooling a sample of the solution until the sample becomesnon-homogeneous and separates into two phases. The temperature at whichthe first tendency of separation or turbidity is observed is the T_(s).

[0049] 3. Cool the solution to a temperature below the T_(s) at whichtwo phases form,

[0050] 4. Separate the two phases. The lower phase will contain thehighest molecular weight material.

[0051] Using the above method, it is possible, first to remove the highmolecular weight poly-HEMA, and then to remove the poly-HEMA that has amolecular weight that is lower than the desired range. So, for example,the poly-HEMA/solvent mixture is cooled to a few degrees below theT_(s), allowed to separate into two phases, the upper phase containinglow and medium molecular weight poly-HEMA is siphoned off, cooled to alower temperature to achieve a second separation, the second upperphase, which is a thin solution of the low end fraction, is siphonedoff, and the second lower phase, which primarily contains the desiredlow polydispersity poly-HEMA is worked up. The poly-HEMA in the secondlower phase has a considerably reduced amount of high and low molecularweight poly-HEMA.

[0052] For many applications the polymer obtained from this second lowerphase can be used directly. It is possible to carry out a furtherfractionation by repeating the process described above.

[0053] It is possible to influence the T_(s), by proper choice ofsolvent. For example a solution of poly-HEMA in isopropanol will have ahigher T_(s) than a solution in which the solvent is ethanol. By usingmixtures of solvents it is possible to fine tune the temperature atwhich the best separation can be obtained. Suitable solvents which areuseful for fractionation based upon T_(s) include solvents having lowδ_(H) and the δ_(P) parameters, and preferably δ_(H) less than about 4and the δ_(P) less than about 6. Specific examples include hexane andheptane. This may be useful when the purpose is to remove the low-endmaterial from a solution from which the high molecular weight poly-HEMAhas already been removed. To obtain a renewed separation it is oftenrequired to use temperatures well below room temperature such as fromabout 5 to about 10° C. In such cases it can be practical to add a minoramount of a solvent that raises the separation temperature to a morepractical level, for example where the poly-HEMA solution remains aliquid, e.g., between about ambient and about 50° C.

[0054] The T_(s) is also influenced by the concentration andpolydispersity of the poly-HEMA in the solution. For instance, theremoval of high and low molecular weight poly-HEMA may result in apoly-HEMA that in solution gives a higher T_(s) than the original, morepolydisperse material. Also dilution to lower concentration may lead toseparation at higher temperature. It is possible that the reason forthis is that a certain concentration of low molecular weight poly-HEMAchains may help to keep the longer chains in solution.

[0055] By manipulation of polymer concentration, choice of solvent, andseparation temperature it is possible to influence both the volume ratiobetween the two phases as well as the concentration of poly-HEMA ineach.

[0056] Suitable temperature ranges for the fractionation include thosebetween about 5 to about 50° C. Suitable standing times include betweenabout 1 hour to about 7 days.

[0057] The amount of poly-HEMA discharged with the high molecular weightmaterial should be from about 10 weight % to about 50 weight % of thepoly-HEMA. Removal of about 5 to about 40 weight % with the lowmolecular weight fraction is often practical, and the yield of poly-HEMAwith low polydispersity after removal of high and low molecular weightmaterial may be about 10 to about 90% and preferably about 30 to about80% of the original amount. The reduced yield is however a minorconsideration since the poly-HEMA produced by free radicalpolymerization is relatively inexpensive and the fractionated materialis of high value in many applications.

[0058] In a preferred poly-HEMA the amount of polymer molecules withmolecular weight less than about 15,000 is less than about 10%,preferably less than about 5% and more preferably less than about 2%.

[0059] It will be evident from the description and the examples that thefractionation methods are flexible and can be adapted according to thenature of the specific polymer. The conditions required to obtain thedesired degree of polydispersity can easily be determined by simplesmall-scale experiments using the above disclosure.

[0060] Suitable temperature ranges include about 5 to about 50° C.Suitable standing times include between about 1 hour and to about 7days.

[0061] One important advantage of poly-HEMA prepared by free radicalpolymerization followed by fractionation is that the initiators andother additives used in the polymerization have been used for manyyears, and their toxicology is known and well described. This isimportant when the poly-HEMA, the crosslinkable prepolymer or theresulting hydrogel is used in a medical application.

[0062] In one embodiment only the low molecular weight fraction isremoved from the poly-HEMA. This can be done by the solvent/non-solventprocess described above. In a preferred embodiment the low molecularweight material is removed during the washing step after the poly-HEMAhas been functionalized.

[0063] The poly-HEMA of the present invention may also be formeddirectly by anionic polymerization or controlled free radicalpolymerization, such as with a TEMPO type polymerization, ATRP (atomtransfer radical polymerization), GTP (Group transfer polymerization),and RAFT (Reversible addition-fragmentation chain transferpolymerization).

[0064] General conditions for the above processes are known anddisclosed in “Controlled Radical Polymerization”; KrzysztofMatyjaszewski, editor; ACS Symposium Series 685; American ChemicalSociety, Washington, D.C.; 1998. For example, for anionic polymerizationthe desired silyl protected monomer is dissolved in a suitable solvent,such as THF solution. The reaction is conducted at reduced temperature,between about −60° C. and about −90 ° C. using known initiators such as1,1-diphenylhexyllithium as initiator. The polymerization may beterminated by conventional means, such as, but not limited to degassedmethanol.

[0065] The poly-HEMA compositions having a specific molecular weightrange and polydispersity can be used to make crosslinkable prepolymerswith well-defined polydispersity and molecular weight. As but oneexample, the crosslinkable prepolymers can have acrylic groups which canbe crosslinked by UV in an extremely short time to form contact lenseswith very desirable properties so far unobtainable by conventionalmethods.

[0066] The poly-HEMA is functionalized to form a crosslinkableprepolymer by attaching a crosslinkable functional group thereto.Generally the functional group provides the ability to crosslink andform crosslinked polymers or hydrogels to the prepolymer. Suitablereactants that provide the crosslinkable functional groups have thestructure A-S-F, where A is an attaching group which is capable offorming a covalent bond with a hydroxyl group in the poly-HEMA; S is aspacer and F is a functional group comprising an ethylenicallyunsaturated moiety. Suitable attaching groups, A, include chloride,isocyanates, acids, acid anhydrides, acid chlorides, epoxies,azalactones, combinations thereof and the like. Preferred attachinggroups include acid anhydrides.

[0067] The spacer may be a direct bond, a straight, branched or cyclicalkyl or aryl group having 1 to 8 carbon atoms and preferably 1 to 4carbon atoms or a polyether chain of the formula —(CH₂—CH₂—O)_(n)— wheren is between 1 and 8 and preferably between 1 and 4.

[0068] Suitable functional groups comprise free radical polymerizableethylenically unsaturated moieties. Suitable ethylenically unsaturatedgroups have the formula

—C(R¹⁰)=CR¹¹R¹²

[0069] Where R¹⁰, R¹¹ and R¹² are independently selected from H, C₁₋₆alkyl, carbonyl, aryl and halogen. Preferably R¹⁰, R¹¹ and R¹² areindependently selected from H, methyl, aryl and carbonyl, and morepreferably in some embodiments selected from H and methyl.

[0070] Preferred reactants include methacrylic acid chloride,2-isocyanatoethylacrylate, isocyanatoethyl methacrylate (IEM), glycidylmethacrylate, cinnamic acid chloride, methacrylic acid anhydride,acrylic acid anhydride and 2-vinyl-4-dimethylazalactone. Methacrylicacid anhydride is preferred.

[0071] Suitable amounts of the crosslinkable functional group attachedto the poly-HEMA include from about 1 to about 20 %, and preferablybetween about 1.5 to about 10 %, and most preferably from about 2 toabout 5% on a stoichiometric basis based upon the amount of availablehydroxyl groups in the poly-HEMA. The degree of functionalization may bemeasured by known methods such as determination of unsaturated groups orby hydrolysis of the bond between the functional reactant and thepolymer followed by determination of the released acid by HPLC.

[0072] Depending on the attaching group selected, the functionalizationmay be conducted with or without a conventional catalyst. Suitablesolvents include polar, aprotic solvents which are capable of dissolvingthe poly-HEMA at the selected reaction conditions. Examples of suitablesolvents include dimethylformamide (DMF), hexamethylphosphoric triamide(HMPT), dimethyl sulfoxide (DMSO), pyridine, nitromethane, acetonitrile,dioxane, tetrahydrofuran (THF) and N-methylpyrrolidone (NMP). Preferredsolvents include formamide, DMF, DMSO, pyridine, NMP and THF. When IEMis used the catalyst is a tin catalyst and preferably dibutyl tindilaurate.

[0073] The functionalization reaction mixture may also contain ascavenger capable of reacting with moieties created by thefunctionalization. For example, when acid anhydrides are used as theattaching group, it may be beneficial to include at least one tertiaryamine, a heterocyclic compound with an aprotic nitrogen or other lewisbases to react with the carboxyl group which is generated. Suitabletertiary amines include pyridine, triethylenediamine and triethylamine,with triethylamine being preferred. If included the tertiary amine maybe include in a slight molar excess (about 10%). In a preferredembodiment the solvent is NMP, the reactant is methacrylic acidanhydride, acrylic acid anhydride or a mixture thereof and triethylamineis present. The most preferred reactant is methacrylic acid anhydride.

[0074] The reaction is run at about room temperature. Each functionalgroup will require a specific temperature range, which is understood bythose of skill in the art. Ranges of about 0° C. and 50° C. andpreferably about 5° C. and about 45° C. are suitable. Ambient pressuresmay be used. For example, when the crosslinkable functional group is anacid anhydride the functionalization is conducted at temperaturesbetween about 5° C. and about 45° C. and for times ranging from about 20to about 80 hours. It will be appreciated by those of skill in the art,that ranges outside those specified may be tolerated by balancing thetime and temperatures selected.

[0075] The reaction is run to produce a crosslinkable prepolymer with apoly-HEMA backbone having a molecular weight and polydispersity asdefined above.

[0076] Apart from attaching crosslinkable side groups other side groupsmay provide additional functionality including, but not limited tophotoinitiators for crosslinking, pharmaceutical activity and the like.Still other functional groups may contain moieties that can bind and/orreact with specific compounds when the crosslinked gels are used inanalytical diagnostic applications.

[0077] Once the crosslinkable prepolymer has been formed, substantiallyall unreacted reactants and byproducts should be removed. By“substantially all” we mean that less than about 0.1 weight % remainsafter washing. This can be done by conventional means, such asultrafiltration. However, in the present invention it is possible topurify the cross-linkable prepolymer by swelling the prepolymer withwater and rinsing with water to remove substantially all of theundesired constituents including monomeric, oligomeric or polymericstarting compounds and catalysts used for the preparation of thepoly-HEMA and byproducts formed during the preparation of thecrosslinkable prepolymer. The washing is conducted with deionized waterand conditions are selected to provide a large surface to volume ratioof the crosslinkable prepolymer particles. This can be done by freezedrying the crosslinkable prepolymer, making a thin film from thecrosslinkable prepolymer, extruding the crosslinkable prepolymer intorods, nebulizing the crosslinkable prepolymer solution into thedeionized water, and other like methods, which are know to those skilledin the art.

[0078] The washings may be conducted in batches with about 3 to about 5water replacements at room temperature and the equilibrium time betweenwater replacements can be shortened by washing (extracting) at elevatedtemperatures below about 50° C.

[0079] This process has numerous advantages over methods of the priorart. The water removes impurities which would leach out during storageand use, providing confidence that a pure material, suitable for the enduse, has been produced.

[0080] In one embodiment unfractionated poly-HEMA having polydispersityoutside the preferred range, or poly-HEMA from which only the highmolecular weight material has been removed, is functionalized and thefunctionalized material is washed repeatedly with large volumes of waterto remove reactants and poly-HEMA of low molecular weight. By thismethod a very pure functionalized poly-HEMA of low polydispersity suchas below 2.0, preferred below 1.7 and more preferred below 1.5, can beobtained. The functionalized crosslinkable poly-HEMA obtained by thismethod comprises less than 10%, preferably less than 5% and morepreferably less than 2% of poly-HEMA of molecular weight smaller thanabout 15,000.

[0081] The extent to which the small molecules should be removed dependson the degree of functionalization and the intended use. Preferably,during cure, all poly-HEMA molecules should become bound into thepolymer network by at least two covalent bonds. Due to the statisticalnature of the functionalization and the cure, the probability that apoly-HEMA molecule will be bound into the polymer network through onlyone covalent bond or none at all increases with decreasing peakmolecular weight and decreasing degree of functionalization.

[0082] For lower functionalization relatively more of the low molecularweight material should be removed. The correct amount can easily bedetermined by experiments comparing removal and mechanical properties.

[0083] Once the crosslinkable prepolymer has been purified it is thendissolved in a water replaceable diluent to form a viscous solution. Thediluent should function as a medium in which the crosslinkablefunctionalized poly-HEMA prepolymer can be dissolved and in which thecrosslinking reaction or cure can take place. In all other respects thediluent should be non-reactive. Suitable diluents include those capableof dissolving, at or below 65° C., between about 30 weight % to about 60weight % crosslinkable prepolymer based upon the total weight of theviscous solution. Specific examples include alcohols having one to fourcarbon atoms, and preferably methanol, ethanol, propanol and mixturesthereof. Water may be used as a co-diluent in minor amounts such as lessthan about 50% of the total diluent. For hydrogels, diluents should beadded to the crosslinkable prepolymer in an amount which is approximateor equal to the amount of water present in the final hydrogel. Diluentamounts between about 40 and about 70 weight % of the resulting viscoussolution are acceptable.

[0084] Viscous solutions of the present invention have a viscosity ofabout 50,000 cps to about 1×10⁷ cps at 25° C., preferably of about100,000 cps to about 1,000,000 cps at 25° C., and more preferably ofabout 100,000 cps to about 500,000 cps at 25° C.

[0085] Preferably the diluents are also safe for the article's intendedend use. So, for example, when the article being formed is a contactlens, the solvent should preferably be safe for ocular contact andophthalmically compatible. This is particularly important for diluentsthat will not or will only partially be removed from the resultingarticle prior to use. Diluents that will not be evaporated from theresulting article should have the capability to bring the Tg of theviscous solution to below about room temperature, (preferably a Tg lessthan about −50° C.) and low vapor pressures (boiling point above about180° C). Examples of biocompatible diluents include polyethyleneglycols, glycerol, propylene glycol, dipropylene glycol mixtures thereofand the like. Preferred polyethylene glycols have molecular weightsbetween about 200 and 600. Use of biocompatible diluents allows theremoval of a separate, washing/evaporation step to remove the diluents.

[0086] Low boiling diluents may also be used, but may require anevaporation step for diluents which are not compatible with the intendeduse environment. Low boiling diluents are polar and generally have lowboiling points (less than about 150° C.), which make removal viaevaporation convenient. Suitable low boiling diluents include alcohols,ethers, esters, glycols, mixtures thereof and the like. Preferred lowboiling diluents include alcohols, ether alcohols, mixtures thereof andthe like. Specific examples of low boiling diluents include3-methoxy-1-butanol, methyl lactate, 1-methoxy-2-propanol,1-ethoxy-2-propanol, ethyl lactate, isopropyl lactate, mixtures thereofand the like.

[0087] A polymerization initiator may also be added. The initiator maybe any initiator that is active at the processing conditions. Suitableinitiators include thermally activated, photoinitiators (including UVand visible light initiators) and the like. Suitable thermally activatedinitiators include lauryl peroxide, benzoyl peroxide, isopropylpercarbonate, azobisisobutyronitrile, 2,2-azobis isobutyronitrile,2,2-azobis 2-methylbutyronitrile and the like. Suitable photoinitiatorsinclude aromatic alpha hydroxyketone or a tertiary amine plus adiketone. Illustrative examples of photoinitiator systems are1-hydroxycyclohexylphenyl ketone,2-hydroxy-methyl-1-phenyl-propan-1-one, benzophenone, thioxanthen-9-one,a combination of camphorquinone and ethyl-4-(N,N-dimethylamino)benzoateor N-methyldiethanolamine, hydroxycyclohexyl phenyl ketone,bis(2,4,6-trimethylbenzoyl)-phenyl phosphine oxide andbis(2,6-dimethoxybenzoyl)-2,4,4-trimethylpentyl phosphine oxide,(2,4,6-trimethylbenzoyl)diphenyl phosphine oxide and combinationsthereof and the like. Photoinitiation is a preferred method andbis(2,6-dimethoxybenzoyl)-2,4,4-trimethylpentyl phosphine oxide,bis(2,4,6-trimethylbenzoyl)-phenyl phosphine oxide and2-hydroxy-methyl-1-phenyl-propan-1-one are preferred photoinitiators.Other initiators are known in the art, such as those disclosed in U.S.Pat. No. 5,849,841, at column 16, the disclosure of which isincorporated herein by reference.

[0088] Other additives which may be incorporated in the prepolymer orthe viscous solution include, but are not limited to, ultravioletabsorbing compounds, reactive dyes, organic and inorganic pigments,dyes, photochromic compounds, release agents, antimicrobial compounds,pharmaceuticals, mold lubricants, wetting agents, other additivesdesirable to maintain a consistent product specification, (such as butnot limited to TMPTMA) combinations thereof and the like. Thesecompositions may be added at nearly any stage and may be copolymers,attached or associated or dispersed.

[0089] The viscous solution should preferably not contain compounds suchas free monomers which can, during cure, give polymer material which isnot bound up in the network and/or will give residual extractablematerial.

[0090] In a solution of a polymer the rheological properties are to ahigh degree determined by the longest molecules. The poly-HEMA of thepresent invention is low in molecules of very high molecular weight andthis gives their solutions a number of desirable properties.

[0091] The viscous solutions of the present invention have beneficiallyshort relaxation times. Relaxation times are less than about 10 seconds,preferably less than about 5 seconds and more preferably less than about1 second. Short relaxation times are beneficial because prepolymershaving them are capable of relieving flow induced stresses prior tocuring so the cured polymer network is free of locked-in stresses. Thisallows the viscous solutions of the present invention to be processedwithout long “hold” times between closing the mold and curing theviscous solution.

[0092] The poly-HEMA of the present invention may be used as startingmaterials for making functionalized poly-HEMA prepolymers and hydrogels,binders for tints in contact lenses, binders in inks for tampo and inkjet printing and the like.

[0093] The viscous solution of the present invention may be used to forma variety of articles. For example molded articles, profiles, preforms,parisons, films, fiber, tubing, sheet, coatings and the like. Morespecifically, suitable articles include biomedical devices, medicalgrade coatings, polymers with reactive groups or biological assaymarkers which are bound to the polymer and the like.

[0094] As used herein, a “biomedical device” is any article that isdesigned to be used while either in or on mammalian tissues or fluid.Examples of these devices include but are not limited to catheters,implants, stents, fluid collection bags, sensors, hydrogel bandages,tubing, coatings for any of the preceding articles, carriers forantibiotic, diagnostic and therapeutic agents, and ophthalmic devices. Aclass of preferred biomedical devices include ophthalmic devices,particularly contact lenses.

[0095] As used herein, the terms “lens” and “ophthalmic device” refer todevices that reside in or on the eye. These devices can provide opticalcorrection, wound care, drug delivery, diagnostic functionality or maybe cosmetic. The term lens includes but is not limited to soft contactlenses, hard contact lenses, intraocular lenses, overlay lenses, ocularinserts, optical inserts and spectacle lenses.

[0096] A number of methods may be used to form the articles of thepresent invention including injection molding, extrusion molding, spincasting, extrusion coating, closed mold molding, cast molding,combinations thereof and the like. The forming method will be followedby a curing step, described below.

[0097] In one embodiment of the present invention the prepolymersolution is used to form a lens. The preferred method for producing alens from the viscous solution of the present invention is via directmolding. A lens-forming amount of the prepolymer solution is dispensedinto a mold having the shape of the final desired hydrogel. The mold maybe made from any suitable material including, without limitation,polypropylene, polystyrene and cyclic polyolefins.

[0098] By “lens-forming amount” is meant an amount sufficient to producea lens of the size and thickness desired. Typically, about 10 to about50 μl of viscous solution is used per contact lens. Next the mold partsare assembled such that the viscous liquid fills the mold cavity. Abenefit of the present invention is that the hold time necessary betweenassembling the mold parts and curing is very short.

[0099] We have found that to avoid introducing unwanted stresses intothe final article, it is necessary to allow the viscous solution to restin the closed mold for a period two to three times longer than theviscous solution's relaxation time. The viscous solution of the presentinvention have beneficially short relaxation times at room temperature(less than about 10 seconds, preferably less than about 5 seconds, andmore preferably less than about 1 second) which allow for hold timeswhich are generally less than about 30 seconds, preferably less thanabout 10 seconds and more preferably less than about 5 seconds.

[0100] An additional benefit of the short holding times of the presentinvention is that they minimize oxygen diffusion into the crosslinkableprepolymer from the mold parts. Diffusion of oxygen can impair thecuring process at the surface of the article. It will be appreciatedthat the viscous solution may be held for longer than the timesspecified in low oxygen content molds with minimal or no negative impactother than slower production times.

[0101] The mold containing the viscous solution is exposed to ionizingor actinic radiation, for example electron beams, X-rays, UV or visiblelight, ie. electromagnetic radiation or particle radiation having awavelength in the range of from about 280 to about 650 nm. Also suitableare UV lamps, HE/Cd, argon ion or nitrogen or metal vapor or NdYAG laserbeams with multiplied frequency. The selection of the radiation sourceand initiator are known to those of skill in the art. Those of skill inthe art will also appreciate that the depth of penetration of theradiation in to the viscous solution and the crosslinking rate are indirect correlation with the molecular absorption coefficient andconcentration of the selected photoinitiator. In a preferred embodimentthe radiation source is selected from UVA (about 315-about 400 nm), UVB(about 280-about 315) or visible light (about 400 -about 450 nm), athigh intensity. As used herein the term “high intensity” means thosebetween about 100 mW/cm² to about 10,000 mW/cm². The cure time is short,generally less than about 30 seconds and preferably less than about 10seconds. The cure temperature may range from about ambient to elevatedtemperatures of about 90° C. For convenience and simplicity the curingis preferably conducted at about ambient temperature. The preciseconditions will depend upon the components of lens material selected andare within the skill of one of ordinary skill in the art to determine.

[0102] The cure conditions must be sufficient to form a polymer networkfrom the crosslinkable prepolymer. The resulting polymer network isswollen with the diluent and has the form of the mold cavity.

[0103] Once curing is completed, the molds are opened. Post moldingpurification steps to remove unreacted components or byproducts areeither simplified compared to conventional molding methods, or are notnecessary in the present invention. If a biocompatible diluent is usedno washing or evaporating step is required at this phase either. It isan advantage of the present invention that when a biocompatible diluentis used, both post molding extraction and diluent exchange steps are notrequired. If a low boiling diluent is used, the diluent should beevaporated off and the lens hydrated with water.

[0104] The resulting lenses comprise a polymer network, which whenswelled with water becomes a hydrogel. Hydrogels of the presentinvention may comprise between about 20 to about 75 weight % water, andpreferably between about 20 to about 65 weight % water. The hydrogels ofthe present invention have excellent mechanical properties, includingmodulus and elongation at break. The modulus is at least about 20 psi,preferably between about 20 and about 90 psi, and more preferablybetween about 20 and about 70 psi.

[0105] The elongation at break is greater than about 100% and preferablygreater than about 120%. Due to the absence of loose polymer chains, thehydrogels will after high relative deformation such as 100% return totheir original shape without distortion. The hydrogels of the presentinvention are also free from visible haze and distortion. The foregoingcombination of properties makes the hydrogels of the present inventionexcellently suited for use as ophthalmic devices and particularly softcontact lenses.

[0106] Lenses thus produced may be transferred to individual lenspackages containing a buffered saline solution. The saline solution maybe added to the package either before or after transfer of the lens.Lenses containing a biocompatible diluent will, upon standing in thesaline solution, exchange the diluent with water, forming the desiredhydrogel. This may also be accomplished in a separate step, if desired.While stored in the package, the polymer network will take up a specificamount of water determined by the hydrophilicity of the polymer. Theequilibrium water content (expressed in weight % of the hydrated lens)may be higher or lower than the amount of the diluent present duringcuring. Typical hydrogels which are useful for making contact lensescomprise between about 20 and about 75 weight % water. The hydrogel maythus expand or contract when in equilibrium in water. It is, however, anessential feature that although the size may change, the shape of thefully hydrated article will be a true reproduction of the shape of themold cavity.

[0107] In a preferred embodiment the amount of diluent is carefullychosen to give a lens that will not expand or contract when inequilibrium in water and is a true 1:1 reproduction of the mold cavity,which is an advantage for predicting the optical parameters of theresulting lens.

[0108] Appropriate packaging designs and materials are known in the art.A plastic package is releasably sealed with a film. Suitable sealingfilms are known in the art and include foils, polymer films and mixturesthereof.

[0109] The sealed packages containing the lenses are then sterilized toensure a sterile product. Suitable sterilization means and conditionsare known in the art, and include, for example, autoclaving.

[0110] It will be appreciated by those of skill in the art that othersteps may be included in the molding and packaging process describedabove. Such other steps can include coating the formed lens, surfacetreating the lens during formation (for example via mold transfer),inspecting the lens, discarding defective lenses, cleaning the moldhalves, reusing the mold halves, combinations thereof and the like.Processes and coating compositions are disclosed in of U.S. Pat. Nos.3,854,982; 3,916,033; 4,920,184; and 5,002,794; 5,779,943, 6,087,415; WO91/04283, and EPO 93/810,399, which are incorporated herein byreference.

[0111] The shaped articles of the present invention have very low or notendency to distortion after being removed from the mold. Distortion hasbeen an inherent problem of molded articles formed from functionalizedprepolymers which have a high molecular weight. The presence ofprepolymer chains having molecular weights which are above the rangesspecified in the present invention impart a slow relaxation time to thefunctionalized prepolymer. During curing, the stresses caused by theunrelaxed, long chains are locked into the cured polymer network. Uponremoval from the mold these stresses distort the molded article so thatits shape is no longer a true replica of the mold. The crosslinkableprepolymers of the present invention have short relaxation times, whicheliminates distortion upon molding.

[0112] As used herein the term “hydrogel” means a hydrated crosslinkedpolymeric system that contains water in an equilibrium state. Hydrogelstypically are oxygen permeable and biocompatible, making thempreferential materials for producing biomedical devices and inparticular contact or intraocular lenses.

[0113] In the present application all molecular weights are to beunderstood as molecular weights determined by the gel permeationchromatography (GPC) analysis (also called Size Exclusion Chromatography) using the method developed by K. Almdal of the Risø NationalLaboratories, Denmark (Almdal, K., Absolute Molar Mass DistributionDetermination by Size Exclusion Chromatography. Synthesis of NarrowMolar Mass Distribution Polymers. Characterization of the Molar MassDistribution of Poly(2-Hydroxyethyl Methacrylate) by Size ExclusionChromatography with Coupled Refractive Index and Low Angle Laser LightScattering Detection. Risø-M-2787(v.1) (1989) 141 p).

[0114] In this method a range of polyethylene glycols and polyethyleneoxides with well defined molecular weights are used in the calibrationof the equipment. These standards used for p-HEMA give more accuratevalues for peak molecular wt and Pd than previous methods developed formore hydrophobic polymers. The method is described below.

[0115] Molecular weight may be measured as follows. The SEC equipment iscomposed of a column oven at 40° C., a PE LC-410 pump with PE Nelson900A/D and a series 200 autosampler. The detector is a RI Merck L7490.

[0116] The column combination consists of two TSK-Gel columns fromTosoHaas (G4000PW+G2500PW) and a guardcolumn.

[0117] The eluent is made with methanol-water (75/25 wt/wt) and adjustedto 50 mM sodium chloride (NaCl).

[0118] The flow rate is 0.5 mL/minute. The injection volume is 150 μLand the run time is 60 minutes.

[0119] The calibration curve is obtained with third order regressionusing PEG and PEO of Peak molecular weights ranging from 960000 to 194as standard references. These polymer standards are purchased fromPolymer Laboratories Inc, Amherst Mass. (Calibration kits PEG-10 part No2070-0100; PEO-10 part No 2080-0101). Added standard reference PEG ofPeak molecular weight of 194 gives a flow signal at a well-definedposition, which is used as an internal standard or fixation point. AddedNaCl plays the same role and gives a second fixation point.

[0120] Peak integrations are manually made. Integration start and endpoints are manually determined from significant difference on globalbaseline. Result reports give Mz, Mw, Mn, and Mpeak. in PEG/PEO units.Related values in HEMA units are calculated from the standard reportwith the following mathematical function:

M _(HEMA)=10.^(1,362+0,7854*log M,PEG/PEO)

[0121] The injection solutions are prepared with methanol-water 75/25wt/wt adjusted to 60 mM NaCl to give a polymer concentration of 2 mg/mL.Tetraethylene glycol is added to the sample in a concentration of 1mg/ml in order to give a peak flow reference. The solutions are filteredon 0.5 μm disposable filters before the injection is performed.

[0122] In the present invention polydispersity, Pd of a polymer sampleis defined as Pd=M_(w)/M_(n). The peak molecular weight Mp is themolecular weight of the highest peak in the molecular weightdistribution curve.

[0123] The tensile properties (elongation and tensile modulus) aremeasured using the crosshead of a constant rate of movement type tensiletesting machine equipped with a load cell that is lowered to the initialgauge height. A suitable testing machine includes an Instron model 1122.A dog-bone shaped sample having a 0.522 inch length, 0.276 inch “ear”width and 0.213 inch “neck” width is loaded into the grips and elongatedat a constant rate of strain of 2 in/min. until it breaks. The initialgauge length of the sample (Lo) and sample length at break (Lf) aremeasured. Twelve specimens of each composition are measured and theaverage is reported. Percent elongation is =[(Lf−Lo)/Lo]×100.

[0124] Tensile modulus is measured at the initial linear portion of thestress/strain curve.

[0125] The viscosity is measured using a Haake RS100 RheoStress equippedwith a Haake circulation bath and temperature controller. The complexviscosity is measured by conducting a frequency sweep starting at 40 Hz,going down to 1 mHz and up again to 40 Hz, picking up 3 frequencies perdecade, repeating each frequency three times and waiting one periodbetween each measurement. The measurements are conducted at 25° C.+1°C., using a parallel plate geometry having a 20 mm diameter and a 0.7 mmgap size (sample thickness), which corresponds to a sample volume of ca.0.22 mL. With reference to Cox-Mertz rule (John Ferry, Visco-elasticproperties of polymers, 3^(rd) edition, McGraw-Hill Book Company,1980.), the reported viscosity number (η) is the low frequency value ofthe complex viscosity (η*).

[0126] The relaxation time is measured using the Haake RS100 RheoStressdescribed above and using a shear stress of 400 Pa. The relaxation timeis obtained by plotting G′ and G″ against the frequency, which willcross each other at a cross over frequency f, in such a way that G″>G′at frequencies below f and G′>G″ at frequencies above f. The relaxationtime=1/f.

[0127] The actual degree of functionalization is determined byhydrolysis of the product and the liberated methacrylic acid is detectedusing HPLC. Hydrolysis samples are prepared from aliquots of themethanolic solution and 1 mL NaOH IM. The hydrolysis is driven at roomtemperature for 12 hours at least. The methacrylic acid amount detectedis compared to the amount of dry polymer contained in the sample to givethe actual degree of functionalization.

[0128] Specifically, the HPLC equipment consists of a column oven at 25°C., a Merck L6000 pump, and a Perkin Elmer LC290 UV detector. The columncombination is composed of a Merck RP 18 column (125 mm/4 mm) and aGuardcolumn.

[0129] The mobile phase is an acetonitrile-water mixture (1/9 wt/wt)adjusted to pH 2.5 with trifluoroacetic acid. The flow rate is fixed to1 mL/minute and the injection volume is 10 μL.

[0130] The detection is carried out at a wavelength of 230 nm. The dataacquisition time is 8 minutes. Series of calibrators are generated fromdiluted solutions of methacrylic acid in mobile phase of concentrationranging from 5 to 25 ppm.

[0131] The injection solutions are prepared from the hydrolysis samplesdiluted with mobile phase and 10 mL HCl, 1M. The solutions are filteredon 13 mm GD/X 0.45 μm Whatmann filters before the injection isperformed.

[0132] The following examples do not limit the invention. They are meantonly to suggest a method of practicing the invention. Thoseknowledgeable in the field of contact lenses as well as otherspecialties may find other methods of practicing the invention. However,those methods are deemed to be within the scope of this invention.

[0133] The following abbreviations are used in the examples. AIBM2,2′-azobis(2-methylbutyronitrile) DABCO triethylene diamine DMAPN,N-dimethylaminopyridine DMF N,N-dimethylformamide DMSO dimethylsulphoxide EOH ethanol GMA glycerol methacrylate HEMA 2-hydroxyethylmethacrylate IPA 2-propanol MAA methacrylic acid MAACl methacryloylchloride MAAH methacrylic acid anhydride NMP 1-methyl-2-pyrrolidone PEGpolyethylene glycol p(TMS-HEMA)poly(trimethylsilyloxyethyl-methacrylate) Py pyridine TEA triethylamineTMS-HEMA trimethylsilyloxyethyl-methacrylate TEG tetraethylene glycol

EXAMPLE 1

[0134] 1911.6 g ethanol, 1056.6 g HEMA monomer, 3.00 g dodecylmercaptan, and 21.00 g methacrylic acid were blended at 25° C. Themixture was poured into a 5-liter stainless steel reactor with athree-blade stirrer, temperature control and a jacket for cooling andheating.

[0135] The mixture was heated to 68° C., and 7.50 g2,2′-azobis(2-methylbutyronitrile) (AMBN) was added. The AMBN dissolvedrapidly, and the reactor was blanketed with a slow stream of nitrogen.The temperature was held at 68° C. for 18 hours to complete conversion.The reactor was heated to 80° C. and kept at this temperature for 22hours to destroy residual initiator and mercaptan. After cooling to roomtemperature a sample was withdrawn and solid content determined byevaporation at 125° C., 3-4 mm Hg for 24 hours. Solid content=37.2%.Mp=76.6 kDalton, Pd=3.75.

[0136] The poly-HEMA solution was diluted with ethanol to give a 10%solution of poly-HEMA in ethanol. The solution became turbid at 24° C.The solution was heated to 40° C. to make it homogenous and then allowedto stand at about 21° C.

[0137] After three days the solution had separated into two clearphases.

[0138] The two phases were separated and analyzed: TABLE 2 FractionAmount Solid Mp ID Vol. % w % kDalton Pd Top 80 8.6 64.0 2.8 Bottom 2015.6 144 3.34

[0139] The bottom fraction rich in high molecular weight polymer wasdischarged.

[0140] The top fraction was isolated and set at 8° C. for furtherfractionation. After 24 hours the solution had separated into twophases. The top fraction constituted 85% by volume of the total andcontained 2.5 ww % poly-HEMA. The bottom phase constituted 15% vol. ofthe total solution and contained 35.7 ww % poly-HEMA. Mp 83.8 kDaltonPd=2.18. This fraction was isolated for functionalization.

EXAMPLE 2

[0141] HEMA monomer (with an impurity level lower than 0.8% purchasedfrom Rohm) was mixed with triethylamine (≧99.5% pure, from Fluka) andpetrol ether (bp 40-60° C.) passed through aluminum oxide and reactedwith trimethyl chlorosilane (≧99.0% pure, from Fluka) to obtaintrimethylsilyloxyethyl-methacrylate (TMS-HEMA). TMS-HEMA was purified bydistillation from calciumhydride (once) and triethylaluminum (electronicgrade, from Aldrich) (twice).

[0142] The polymerization of TMS-HEMA was carried out in THF (abs.puriss.), solution (Fluka) at −78° C. using 1,1-diphenylhexyl lithium asinitiator and resulted in a quantitative yield. The polymerization wasterminated by degassed methanol. The polymer was isolated by adding theTHF solution of poly(trimethylsilyloxyethyl-methacrylate) p(TMS-HEMA) toa large excess of water.

[0143] The polymer had a peak molecular weight of 63 kD, Mw=75 kD and apolydispersity of 1.6.

EXAMPLE 3

[0144] 1619 g ethanol, 176.5 g HEMA monomer, and 3.60 g methacrylic acid(MAA) were blended at 25° C. The mixture was poured into a 3-liter glassreactor with a stirrer, temperature control and a jacket for cooling andheating.

[0145] The mixture was heated to 68° C., and 1.26 g AMBN was added. TheAMBN dissolved rapidly, and the reactor was blanketed with a slow streamof nitrogen. The temperature was held at 68° C. for 20 hours to completeconversion. After cooling to room temperature the polymer solution wasdiluted with ethanol to give a 10% solution of poly-HEMA in ethanol. TheMp was 70 kD and Pd was 3.33 before fractionation. After addition of 2%hexane the solution had a cloud point of 31° C. The polymer wasfractionated in Example 10.

EXAMPLE 4

[0146] 1625 g ethanol, 108.4 g HEMA monomer, and 72.8 g glycerolmethacrylate were blended at 25° C. The mixture was poured into a3-liter glass reactor with a stirrer, temperature control and a jacketfor cooling and heating.

[0147] The mixture was heated to 74° C., and 1.29 g AMBN was added, andthe reactor was blanketed with a slow stream of nitrogen. Thetemperature was held at 74° C. for 20 hours to complete conversion.After cooling to room temperature the polymer solution was diluted withethanol to give a 10% solution of poly-(HEMA-co-GMA) in ethanol. The Mpwas 56 kD and Pd was 2.35. The solution had a cloud point of 35° C. andwas allowed to fractionate for 3 days at 33° C. The top fraction wassiphoned off and the bottom fraction was discarded. To the top fractionwas added 2% heptane. This gave a cloud point of 49° C. After three daysat 29° C. a new top fraction had formed and was discarded. The bottomfraction containing 64% of the original polymer was isolated, and thepolymer was found to have a Mp of 66 kD and a Pd of 2.1. This polymerwas functionalized in Example 21.

EXAMPLES 5-9

[0148] The polymerization reaction of Example 3 was repeated atdifferent temperatures and using the solvents shown in Table 3, below.The results are given in Table 3 and show that by using this method agood control of molecular weight is obtained. TABLE 3 Ex. # T (° C.)Solvent Mp (kD) Pd 5 82 2-propanol 35 3.4 6 78 2-propanol 40 3.4 7 74Ethanol 50 2.6 8 72 Ethanol 60 3.6 9 68 Ethanol 70 3.3

EXAMPLE 10

[0149] 800 g of the solution prepared in Example 3 was heated to 40° C.to make it homogenous and then allowed to stand at 28° C. After fivedays the solution had separated into two clear phases. The top phasecontaining 77.1% of the polymer was siphoned off and the bottom phasewas discarded.

[0150] The amount of hexane in the top phase was adjusted to 7%, whichresulted in a cloud point of 54° C. The solution was heated to 57° C. tomake it homogenous and then allowed to stand at 29° C. After four daysthe solution had separated into two clear phases. The top phasecontaining the low molecular weight fraction of the polymer was siphonedoff and the bottom phase was given a third fractionation. This time thehexane concentration was adjusted to 8% and the solution was allowed tostand for four days at 30° C. The top phase containing the low molecularweight fraction of the polymer was siphoned off and the polymer in thebottom phase was isolated for functionalization. The results of thefractionation are shown in Table 4, below. TABLE 4 M_(W) K Dalton M_(p)K Dalton Pd Unfractionated 98 70 3.33 p-HEMA Fractionated p- 97 76 1.51HEMA

EXAMPLE 11

[0151] A poly-HEMA with nominal 2% MAA was prepared as in Example 3 andfractionated as described in Example 10. The amount of MAA in thenon-fractionated and fractionated material was determined as describedin ISO standard (3682-1983 (E)), and is shown in Table 5, below. TABLE 5M_(W) (kD) M_(p) (kD) Pd % MAA Unfractionated 98 70 3.33 1.8 p-HEMAFractionated p- 97 76 1.51 1.8 HEMA

[0152] The MAA content in the non-fractionated copolymer is equal to theMAA content found in the fractionated copolymer. This shows that thefractionation process separates the polymer by molecular weight only andnot by composition.

EXAMPLE 12

[0153] 9.09 g of the poly-HEMA formed and isolated in Example 2 wasdried by evaporation at 125° C., 3 mm Hg for 24 hours and then dissolvedby slight warming in pyridine to make a 10% w/w solution. The solutionwas cooled in an ice bath and 400 μL of methacryloyl chloride(corresponding a target-value degree of esterfication of 6 mol percentof the OH-groups in the poly-HEMA) was added. The major part of thepyridine was then removed under vacuum at 25-30° C., and thefunctionalized copolymer was contacted with deionized water to dissolveresidual pyridine and other low molecular weight materials. The waterwas decanted, and the washing repeated until there was no residualpyridine detectable with an HPLC system.

[0154] The functionalized polymer had a MP of 62 kD and a Pd of 1.6.

EXAMPLE 13

[0155] 110 mL of anhydrous 1-methyl-2-pyrrolidone (NMP) (water≦0.01%)was added to a total of 13.6 g of dry p(HEMA-co-MAA) from Example 1,which had been dried under vacuum for 12 hours at 100° C. The reactionflask with a magnetic stirrer was kept under a dry nitrogen atmosphere.A 2% solution of methacrylic acid anhydride 94% in anhydrous NMP (24.7mL, 0.003 moles) was added drop wise over a 2-3 minute period.Triethylamine (0.45 mL, 0.003 moles) was added, and the flask contentwas then heated, while stirring, to 20 35° C. for 48 hours.

[0156] The temperature was decreased to 25° C. and 200 mL of deionisedwater was added. The crude reaction mixture was then poured into 400 mLaqueous HCl (0.1M pH=1.5). 4L of deionised water was added inducinginstantaneous precipitation. After the precipitate had been rinsed withwater, it was dissolved in 100 mL of ethanol. A second precipitation wasmade with 1L of water and HCl (pH=1.5). The precipitate was soaked in anextra litre of water for several hours to remove any remaining acid.

[0157] Finally the precipitate was dissolved in methanol to give a clearsolution.

EXAMPLE 14

[0158] 4.38 grams of an unfractionated HEMA-MAA copolymer was dried byevaporation at 125° C., 3 mm Hg for 24 hours and then dissolved in DMF(99+%, ≦0.1% H₂O) to give a 20% w/w solution. To obtain anesterification of approximately 3% of the copolymer's hydroxyl groups,1.08 mmol of methacrylic anhydride (94% pure) was mixed with 8 mL DMF,and then added to the polymer solution. Triethylamine (1.08 mmol, ≧99.5%pure from Fluka) was subsequently added. The mixture was allowed toreact for 20 hours at 30° C., after which the reaction was stopped byadding 2 mL of water. Glycerol (10 g) was added to the polymer solutionbefore the DMF was distilled off (30° C., 0.5 mbar for 2 hours).

[0159] The functionalized copolymer was contacted with water to dissolveresidual DMF and other low molecular weight materials. The water wasdecanted, and the washing repeated until there were no traces of DMF.The degree of functionalization was determined to be 2.2%, and Mpeak=41kD, and Pd=2.8. When molded into a hydrogel using the methods similar toExample 22 the following mechanical properties were found: Modulus: 11±2psi. Elongation 120±25. The properties are relatively poor due to thehigh Pd.

EXAMPLES 15-20

[0160] Poly-HEMA prepared as in Example 1 (unfractionated) wasfunctionalized using the method described in Example 13 (Examples 15 and16). Poly-HEMA prepared as in Example 1 was fractionated using themethod described in Example 10 and then functionalized using the methoddescribed in Example 13 (Examples 17 and 18). Lenses were made from thepolymers from fractionated and un-fractionated functionalized poly-HEMAusing the methods of Example 22 and 61% w/w tetraethylene glycol as thediluent. The viscous solutions were cured according to the methods ofExample 22. The results are shown in Table 6, below. TABLE 6 HEMA/MAApolymer Lens properties Mp Functionalized polymer Modulus Elongation ExkD Pd Mp Pd psi % 15 40 3.48 48 1.67 32 76 16 53 3.59 62 1.88 33 90 1744 1.35 45 1.4 37 109 18 64 1.7 70 1.59 40 106

[0161] It can be seen that the method employed for functionalization canreduce the polydispersity to an acceptable value. Generally the washingstep removes the smallest poly-HEMA molecules. The lens propertiesindicate that a functionalized polymers having lower polydispersitiesdisplay better mechanical properties.

EXAMPLE 21

[0162] 3.22 grams of a GMA-HEMA copolymer formed and isolated in Example4 was dried by evaporation at 125° C., 3 mm Hg for 24 hours and thendissolved in DMF (99+%, ≦0.1 % H₂O) 20% w/w solution. To obtain anaverage esterification of approximately 2.4 out of every 100 units, 0.74mmol of methacrylic anhydride (94% pure from Fluka) was mixed with 6 mLDMF, and then added to the polymeric solution. Triethylamine (0.74 mmol,≧99.5% pure, from Fluka) was subsequently added to the polymer solution.The reaction mixture was allowed to react for 20 hours at 30° C., afterwhich the reaction was stopped by adding 2 mL of water. 10 g of glycerolwas added to the polymer solution before the DMF was distilled off (30°C., 0.5 mbar for 2 hours).

[0163] The functionalized copolymer was contacted with deionized waterto dissolve residual DMF and other low molecular weight materials. Uponcooling below approximately 5° C., the functionalized polymerprecipitated, and the aqueous phase was decanted. Methanol was added todissolve the functionalized polymer. The degree of functionalization wasfound to be 2.3, which corresponds to 90% of the target value. Thefunctionalized polymer was dissolved with tetraethylene glycol to make amolding solution containing 39% w/w solids using the method of Example22. Lenses were made as described in Example 22. The resulting hydrogellenses had the following mechanical properties (at equilibrium watercontent of 65%) Modulus 18±1 psi. Elongation 120±25%.

EXAMPLE 22

[0164] The solution of the HEMA-2%MAA copolymer from Example 13 wastransferred through a 25 mm GD/X 0.45 mm Whatmann filter to a syringeand mixed with tetraethylene glycol (99+% pure, from Fluka) to give amolding solution containing 39% w/w dry prepolymer, 60.5% tetraethyleneglycol and 0.5% w/w Darocur 1173 photoinitiator was added. The blend wasmixed. By applying a controlled vacuum to the syringe, the low boilingsolvents were removed. The cylinder was centrifuged to bring all thesolution down into the outlet end. The barrel was inserted into thecylinder and pushed down until it was in contact with the moldingsolution while keeping a temporary passage for the air to escape. Thesyringe containing the molding solution was placed in a fixture where acontrolled force was applied to the barrel and about 50 mg of thesolution was dosed into the lower part of a contact lens mold made ofpolystyrene. The upper part of the mold was put in place and the moldwas closed and the parts were held together for 5 seconds by applicationof a 10 kg load.

[0165] The closed mold was placed on a conveyor belt running 1 m/sec.,and the mold passed under a high intensity UV lamp focused 20 mm abovethe conveyor for less than about 10 seconds. The maximum intensity was 5W/cm², and the closed mold received 15J/cm² total as detected in theUV-a range by a PowerPuck® UV-spectrophotometer placed next to theclosed mold.

[0166] After curing the lid was removed by hand, and the lens was soakedfor 10 minutes in deionized water. The resulting hydrogel lensesretained their shape as well as their dimensions when the tetraethyleneglycol diluent was replaced with saline water. Thus a 1:1 copy of themold surface was made. A 14.00 mm diameter mold gave a 14.00 mm diameterhydrogel lens.

EXAMPLE 23

[0167] Example 1 was repeated, except that the poly-HEMA solution wasdiluted with ethanol to give a 36% w/w solution in ethanol. Themolecular weight and polydispersity of the resulting poly-HEMA are shownin Table 7, below.

EXAMPLE 24

[0168] Example 1 was repeated, except that the poly-HEMA solution wasdiluted with ethanol to give a 36% w/w solution in ethanol and octylmercaptan was used as the chain transfer agent instead of dodecylmercaptan. The resulting polymer solution was fractionated as describedin Example 10. The molecular weight and polydispersity of the resultingpoly-HEMA are shown in Table 7, below. TABLE 7 Ex # Fractionated Mw (kD)Mp (kD) Pd 23 No 67 48 2.56 24 Ex 10 47 40 1.26

EXAMPLE 25-28

[0169] Example 3 was repeated except that the polymerization temperature(Examples 25-27) and solvent (Example 28) were varied as shown in Table8, below. Example 27 was not fractionated. All other Examples in thisset were fractionated according to Example 10. Molecular weight andpolydispersity are shown in Table 8, below. TABLE 8 Ex # T (° C.)Solvent Mw (kD) Mp (kD) Pd 25 72 EOH 95 64 1.7 26 68 EOH 94 70 1.56 2775 EOH 67 49 2.6 28 74 IPA 52 45 1.39

EXAMPLES 29-37

[0170] The polymers of Examples 23 through 28 were functionalized usingmethods similar to Example 13, with the changes noted in Table 9, below.The percent functionalization, molecular weight and polydispersities arelisted in Table 9. TABLE 9 Prepol % F % F Acyl. Mw Mp Ex # Ex. # targetactual Solvent base agent (kD) (kD) Pd 29 23 10 2.3 DMSO Py MAACI 83 562.18 30 26 8 2.2 NMP TEA MAACI 89 67 1.42 31 28 6 2.9 NMP DMAP MAAH 5648 1.21 32 28 3.4 2.1 NMP TEA* MAACI 63 48 1.30 33 25 3 1.4 NMP Py MAAH89 68 1.43 34 27 10 2.2 NMP DABCO MAACI 82 55 1.79 35 26 3.3 2.9 NMP TEAMAAH 81 111 1.61 36 26 3 2.2 NMP TEA MAAH 84 114 1.66 37 24 3 2.4 NMPTEA MAAH 43 50 1.25

EXAMPLE 38-41

[0171] The functionalized prepolymers made in Examples 33 and 35 through37 were molded into lenses according to Example 22. The modulus,elongation and equilibrium water content are shown in Table 10, below.TABLE 10 Funct. PP Ex. # Ex. # Modulus (psi) Elong. (%) % H₂O 38 33 4462 62 39 35 50 107 58 40 36 20 150 59 41 37 25 160 59

EXAMPLE 42

[0172] Into a syringe, a polymer solution containing 19.5% w/w of theprepolymer from Example 33 and 19.5% w/w of the prepolymer from Example35 were mixed with TEG (99+% pure, from Fluka) and the photo-initiatorDarocur 1173. Upon evaporation of the alcohol, the viscous solutioncontained Darocur 1173 equal to 0.5% w/w, 60.5% w/w TEG, and 19.5% w/wof each of the prepolymers. Hydrogels made of this molding solution andcured as in Example 22 showed the following mechanical properties:Modulus: 27±2 psi. Elongation 186±14%.

EXAMPLE 43

[0173] Into a syringe, a solution of the functionalized prepolymer fromExample 30 was mixed with tetraethylene glycol (99+% pure, from Fluka)and the photo-initiator Darocur 1173. Upon evaporation of low boilingsolvents, the viscous solution contained Darocur 1173 equal to 0.5% w/w,50% w/w tetraethylene glycol, and 49.5% w/w of the functionalizedprepolymer from Example 30. Degassed water was added to give a viscoussolution that contained Darocur 1173 equal to 0.4% w/w, 39% w/wtetraethylene glycol, and 38.6% w/w of a prepolymer and 22% water asco-diluent. Hydrogels made of this molding solution were cured as inExample 22 and gave the following mechanical properties: modulus of 34±7psi and elongation of 136±20%.

EXAMPLE 45

[0174] The bottom fraction (described in Table 2) of the prepolymer inExample 1 rich in the high molecular weight polymer fraction wasfunctionalized using the methods described in Example 9. Thefunctionalized and washed prepolymer was then mixed with TEG using themethods described in Example 22 to give a viscous solution containing50% solids. The relaxation time of this viscous solution was found to be400 seconds at 20° C.

[0175] About 50 mg of this solution was molded into a contact lensaccording to Example 22 using hold times of 200, 400 and 800 seconds at20° C.

[0176] After curing the lids were removed by hand, and the lenses weresoaked for 10 minutes in deionized water. The lenses prepared using holdtimes of 200 seconds and 400 seconds were distorted and had a shape thatdeviated from the mold cavity. The lenses prepared using hold times of800 seconds maintained the spherical shape of the mold and were freefrom distortion.

We claim
 1. A composition comprising poly-HEMA having a peak molecularweight about 25,000 with a polydispersity of less than about 2 to a peakmolecular weight of about 100,000 with a polydispersity of less thanabout 3.8.
 2. The composition of claim 1 wherein said peak molecularweight is between about 30,000 with a polydispersity of less than about2 and about 90,000 with a polydispersity of less than about 3.5.
 3. Thecomposition of claim 1 wherein said peak molecular weight is betweenabout 30,000 with a polydispersity of less than about 2 and about 80,000with a polydispersity of less than about 3.2.
 4. The composition ofclaim 1 wherein said peak molecular weight is between about 25,000 witha polydispersity of less than about 1.5 and about 80,000 with apolydispersity of less than about 3.5.
 5. The composition of claim 1wherein said peak molecular weight is below about and 100,000 and saidpolydispersity is less than about
 2. 6. The composition of claim 1wherein said polydispersity is less than about 1.7.
 7. The compositionof claim 1 wherein said polydispersity is less than about 1.5.
 8. Thecomposition of claim 1 wherein said poly-HEMA is substantially free fromgel particles.
 9. The composition of claim 1 wherein said poly-HEMA is acopolymer comprising HEMA and at least one comonomer.
 10. Thecomposition of claim 9 wherein said comonomer comprises at least onehydrophilic monomer.
 11. The composition of claim 10 wherein said atleast one hydrophilic monomer is selected from vinyl-containingmonomers.
 12. The composition of claim 11 wherein said at least onevinyl containing monomer is selected from the group consisting ofN,N-dimethyl acrylamide, glycerol methacrylate, 2-hydroxyethylmethacrylamide, polyethyleneglycol monomethacrylate, methacrylic acid,acrylic acid, N-vinyl lactams, N-vinyl-N-methyl acetamide,N-vinyl-N-ethyl acetamide, N-vinyl-N-ethyl formamide, N-vinyl formamide,vinyl carbonate monomers, vinyl carbamate monomers, oxazolone monomersand mixtures thereof.
 13. The composition of claim 10 wherein said atleast one hydrophilic monomer is selected from the group consisting ofN,N-dimethyl-acrylamide, glycerol methacrylate, 2-hydroxyethylmethacrylamide, N-vinylpyrrolidone, polyethyleneglycol monomethacrylate,methacrylic acid and acrylic acid and mixtures thereof.
 14. Thecomposition of claim 10 wherein said at least one hydrophilic monomercomprises N,N-dimethyl acrylamide, methacrylic acid and glycerolmethacrylate.
 15. The composition of claim 10 wherein said at least onehydrophilic monomer is present in an amount less than about 50 weight %.16. The composition of claim 10 wherein said at least one hydrophilicmonomer is present in an amount between about 0.5 and 40 weight %. 17.The composition of claim 10 wherein said hydrophilic monomer comprisesglycerol methacrylate in amounts up to about 50 weight %.
 18. Thecomposition of claim 10 wherein said hydrophilic monomer comprisesglycerol methacrylate in amounts between about 25 and about 45 weight %.19. The composition of claim 10 wherein said hydrophilic monomercomprises methacrylic acid in amounts less than about 5 weight %. 20.The composition of claim 10 wherein said hydrophilic monomer comprisesmethacrylic acid in amounts between about 0.5 and about 5.0 weight %.21. The composition of claim 10 wherein said hydrophilic monomercomprises N,N-dimethyl acrylamide in amounts up to about 50 weight %.22. The composition of claim 10 wherein said hydrophilic monomercomprises N,N-dimethyl acrylamide in amounts between about 10 and about40 weight %.
 23. The composition of claim 1 wherein said poly-HEMA ahomopolymer.
 24. The composition of claim 9 wherein said copolymercomprises at least one hydrophobic monomer.
 25. The composition of claim24 wherein said hydrophobic monomer comprises at least onesilicone-containing monomers or macromer having at least onepolymerizable vinyl group.
 26. The composition of claim 25 wherein saidpolymerizable vinyl group comprises 2-methacryloxy.
 27. A methodcomprising the steps of polymerizing, via free radical polymerization,HEMA monomer having less than about 0.5% crosslinker and optionally atleast one hydrophilic or hydrophobic comonomer to form a highpolydispersity poly-HEMA having a peak molecular weight between about25,000 and about 100,000 and a polydispersity greater than about 2.2 andabout 4 respectively, and purifying said high polydispersity poly-HEMAto form a low polydispersity poly-HEMA having a peak molecular weightbetween about 25,000 and about 100,000 and a polydispersity of less thanabout 2 to less than about 3.8 respectively.
 28. The method of claim 27wherein said free radical polymerization is conducted in a solventcapable of dissolving the monomer and the poly-HEMA during thepolymerization, at a temperature between about 40 and about 150° C. andfor a time from about 2 to about 30 hours.
 29. The method of claim 28wherein said solvent is selected from the group consisting of alcohols,glycols, polyols, aromatic hydrocarbons, amides, sulfoxides,pyrrolidones, ethers, esters, ester alcohols, glycoethers, ketones andmixtures thereof.
 30. The method of claim 28 wherein said solvent isselected from the group consisting of methanol, ethanol, isopropanol,1-propanol, methyllactate, ethyllactate, isopropyllactate,ethoxypropanol, glycol ethers, DMF, DMSO, NMP and cyclohexanone.
 31. Themethod of claim 27 wherein said free radical polymerization is conductedat about ambient pressure, at a temperature between about 60 and about90° C.
 32. The method of claim 27 wherein said free radicalpolymerization is initiated via thermal initiation using at least onethermal initiator.
 33. The method of claim 32 wherein said thermalinitiator is selected from the group consisting of lauryl peroxide,benzoyl peroxide, isopropyl percarbonate, azobisisobutyronitrile,2,2-azobis isobutyronitrile, 2,2-azobis 2-methylbutyronitrile andmixtures thereof.
 34. The method of claim 32 wherein said thermalinitiator comprises 2,2-azobis 2-methylbutyronitrile, 2,2-azobisisobutyronitrile and mixtures thereof.
 35. The method of claim 27wherein said purifying step is conducted via temperature control and/orsolvent/non-solvent fractionation using Hansen Solubility parameters.36. The method of claim 35 where said purifying step is conducted viatemperature control comprising the steps of (a) dissolving saidpoly-HEMA in a solvent having Hansen solubility parameters within saidpoly-HEMA's solubility sphere, to form a separation solution; (b)cooling said separation solution to a temperature below the T_(s) sothat at least a lower phase comprising high molecular weight poly-HEMAand an upper phase forms; and (c) removing the lower phase.
 37. Themethod of claim 36 further comprising the step of subjecting said upperphase to further purification via repeating the steps (a) through (c);or adding to said upper phase a non-solvent that decreases at least onesolubility parameter of said separation mixture in amounts sufficient toprecipitate said low polydispersity poly-HEMA from said separationmixture.
 38. The method of claim 35 wherein said purifying step isconducted via solvent/non-solvent fractionation comprising: (a)dissolving said poly-HEMA in a solvent having Hansen solubilityparameters of δ_(D) from about 13 to about 20, δ_(P) from about 5 toabout 18, and δ_(H) from about 10 to about 25 to form a separationsolution; (b) adding, to said separation mixture, a non-solvent thatdecreases at least one solubility parameters of said separation solutionin amounts sufficient to precipitate high molecular weight poly-HEMAfrom said separation solution; and (c) removing said high molecularweight poly-HEMA.
 39. The method of claim 38 further comprising the stepof subjecting said separation solution to further purification viarepeating the steps (a) through (c); or cooling said separation solutionto a temperature below the T_(s) so that at least a lower phasecomprising high molecular weight poly-HEMA and an upper phase forms; andremoving the lower phase.
 40. The method of claim 38 wherein said atleast one solubility parameters comprises the δ_(H) parameter.
 41. Themethod of claim 38 wherein said decrease in at least on solubilityparameter is between about 2 to about 5 units.
 42. A method comprisingthe steps of attaching at least one crosslinkable functional group topoly-HEMA having a peak molecular weight between about 25,000 and about100,000 and a polydispersity of less than about 2 to less than about 3.8respectively under conditions sufficient to covalently bond saidcrosslinkable functional group to the poly-HEMA chain to form acrosslinkable prepolymer.
 43. The method of claim 42 wherein saidcrosslinkable functional group is present in an amount between about 1to about 20% on a stoichiometric basis based upon the amount ofavailable hydroxyl groups in said poly-HEMA.
 44. The method of claim 42wherein said crosslinkable functional group is present in an amountbetween about 1.5 to about 10% on a stoichiometric basis based upon theamount of available hydroxyl groups in said poly-HEMA.
 45. The method ofclaim 42 wherein said crosslinkable functional group is derived from areactant having the structure A-S-F, where A is an attaching group whichis capable of forming a covalent bond with a hydroxyl group in thepoly-HEMA; S is a spacer and F is a functional group comprising anethylenically unsaturated moiety.
 46. The method of claim 45 wherein Ais selected from the group consisting of chloride, isocyanates, acids,acid anhydrides, acid chlorides, expoxies, azalactones, and combinationsthereof.
 47. The method of claim 45 wherein A comprises at least oneacid anhydride.
 48. The method of claim 45 wherein S is selected fromthe group consisting of a direct bond and straight, branched or cyclicalkyl or aryl group having 1 to 8 carbon atoms, and polyethers of theformula —(CH₂—CH₂—O)_(n)— wherein n is between 1 and
 8. 49. The methodof claim 45 wherein S is selected from the group consisting of a directbond, straight, branched or cyclic alkyl group having 1 to 4 carbonatoms and polyethers of the formula —(CH₂—CH₂—O)_(n)— wherein n isbetween 1 and
 4. 50. The method of claim 45 wherein F has the formula—C(R¹⁰)═CR¹¹R¹². And R¹⁰, R¹¹ and R¹² are independently selected fromthe group consisting of hydrogen and methyl.
 51. The method of claim 45wherein said reactant is selected from the group consisting ofmethacrylic acid chloride, 2-isocyanatoethylacrylate, isocyanatoethylmethacrylate, glycidyl methacrylate, cinnamic acid chloride, methacrylicacid anhydride, acrylic acid anhydride and 2-vinyl-4-dimethylazalactone.52. The method of claim 42 wherein at least one functional groupproviding additional functionality other than crosslinking is attachedto said crosslinkable prepolymer.
 53. The method of claim 44 furthercomprising the step of purifying said crosslinkable prepolymer bywashing said prepolymer with water to remove substantially all ofundesired constituents and byproducts residual from steps for makingsaid crosslinkable prepolymer.
 54. The method of claim 53 wherein saidpurifying step comprises the steps of providing a large surface tovolume ratio of the crosslinkable prepolymer, washing said crosslinkableprepolymer with deionized water at or above room temperature.
 55. Themethod of claim 42, further comprising the step of mixing said purifiedcrosslinkable prepolymer with a diluent to form a viscous solutionhaving a viscosity of about 50,000 cps to about 1×10⁷ cps at 25° C. 56.The method of claim 55 wherein said diluent is biocompatible, has a lowTg, low vapor pressure and will dissolve, at or below 65° C., betweenabout 30 weight % to about 60 weight % crosslinkable prepolymer basedupon the total weight of the viscous solution.
 57. The method of claim56 wherein said diluents are selected from the group consisting ofpolyethylene glycols, glycerol, propylene glycol, dipropylene glycol andmixtures thereof.
 58. The method of claim 57 wherein said diluentscomprise polyethylene glycols have molecular weights between about 200and
 600. 59. The method of claim 56 wherein said diluent is polar andcomprises a boiling point less than about 150° C.
 60. The method ofclaim 59 wherein said diluent is selected from the group consisting ofalcohols, ethers, esters, glycols and mixtures thereof.
 61. The methodof claim 59 wherein said diluents are selected from the group consistingof alcohols, ether alcohols and mixtures thereof.
 62. The method ofclaim 59 wherein said diluents are selected from the group consisting of3-methoxy-1-butanol, methyl lactate, 1-methoxy-2-propanol,1-ethoxy-2-propanol, ethyl lactate, isopropyl lactate and mixturesthereof.
 63. The method of claims 59 further comprising the step ofevaporating said diluent after an article is formed and cured from saidviscous solution.
 64. The method of claim 55 wherein said viscoussolution further comprises at least one initiator.
 65. The method ofclaim 64 wherein said initiator comprises at least one photoinitiator,thermally activated initiator and mixtures thereof.
 66. The method ofclaim 64 wherein said initiator is selected from the group consisting ofbis(2,6-dimethoxybenzoyl)-2,4,4-trimethylpentyl phosphine oxide anddiketone, 1-hydroxycyclohexylphenyl ketone.
 67. The method of claim 55wherein said viscous solutions further comprises at least one additivewhich enhances or provides a desired benefit or which reduces oreliminates an undesirable trait in an article made from said viscoussolution.
 68. The method of claim 67 wherein said additive is selectedfrom the group consisting of ultra-violet absorbing compounds, reactivedyes, organic or inorganic pigments, photochromic compounds, releaseagents, mold lubricants, antimicrobial compounds, pharmaceuticalcompounds, wetting agents, additives desirable to maintain a consistentproduct specification and combinations thereof.
 69. The method of claim55 wherein said viscous solution has a relaxation time of less thanabout 10 seconds.
 70. The method of claim 55 wherein said viscoussolution has a relaxation time of less than about 5 seconds.
 71. Themethod of claim 55 wherein said viscous solution has a relaxation timeof less than about 1 second.
 72. The method of claim 42 wherein saidpoly-HEMA is formed via a polymerization method giving lowpolydispersity directly.
 73. The method of claim 72 wherein saidpolymerization method is conducted via free radical livingpolymerization.
 74. A method comprising the steps of attaching at leastone crosslinkable functional group to poly-HEMA having a peak molecularweight between about 25,000 and about 100,000 and a polydispersity ofgreater than about 2.2 to greater than about 4 respectively underconditions sufficient to covalently bond said crosslinkable functionalgroup to the poly-HEMA chain to form a crosslinkable prepolymer andtreating said crosslinkable prepolymer to form a crosslinkableprepolymer having a polydispersity of less than about 2 wherein lessthan 10% of said crosslinkable prepolymer has a molecular weight of lessthan about 15,000.
 75. A composition comprising at least onecrosslinkable prepolymer comprising poly-HEMA having a peak molecularweight between about 25,000 and about 1000,000 and a polydispersity ofless than about 2 to about 3.8 respectively and covalently bondedthereon, at least one cross-linkable functional group.
 76. Thecomposition of claim 75 wherein said crosslinkable functional group ispresent in an amount between about 1 to about 20 % on a stoichiometricbasis based upon the amount of available hydroxyl groups in saidpoly-HEMA.
 77. The composition of claim 75 wherein said crosslinkablefunctional group is present in an amount between about 1.5 to about 10weight % on a stoichiometric basis based upon the amount of availablehydroxyl groups in said poly-HEMA.
 78. The composition of claim 75wherein said crosslinkable functional group is derived from a reactanthaving the structure A-S-F, where A is an attaching group which iscapable of forming a covalent bond with a hydroxyl group in thepoly-HEMA; S is a spacer and F is a functional group comprising anethylenically unsaturated moiety.
 79. The composition of claim 78wherein A is selected from the group consisting of Cl, isocyanates,acids, acid anhydrides, acid chlorides, expoxies, azalactones, andcombinations thereof.
 80. The composition of claim 78 wherein Acomprises at least one acid anhydride.
 82. The composition of claim 78wherein S is selected from the group consisting of a direct bond,straight, branched or cyclic alkyl or aryl groups having 1 to 8 carbonatoms and polyethers of the formula —(CH₂—CH₂—O)_(n)— wherein n isbetween 1 and
 8. 83. The composition of claim 78 wherein S is selectedfrom the group consisting of a direct bond, straight, branched or cyclicalkyl groups having 1 to 4 carbon atoms and polyethers of the formula—(CH₂—CH₂—O)_(n)— wherein n is between 1 and
 4. 84. The composition ofclaim 78 wherein F has the formula —C(R¹⁰)═CR¹¹R¹² wherein R¹⁰, R¹¹ andR¹² are independently selected from the group consisting of hydrogen andmethyl.
 85. The composition of claim 78 wherein said reactant isselected from the group consisting of methacrylic acid chloride,methacrylic acid anhydride, acrylic acid anhydride,2-isocyanatoethylacrylate, isocyanatoethyl methacrylate, glycidylmethacrylate, cinnamic acid chloride and 2-vinyl-4-dimethylazalactone.86. The composition of claim 78 wherein said reactant comprisesmethacrylic acid anhydride.
 87. The composition of claim 78 furthercomprising at least one covalently bound functional group that providesadditional functionality other than crosslinking to said crosslinkableprepolymer.
 88. A viscous solution comprising the crosslinkableprepolymer of claim 75, and a diluent in an amount sufficient to providesaid viscous solution with a viscosity of about 50,000 cps to about1×10⁷ cps at 25° C.
 89. The viscous solution of claim 88 wherein saiddiluent is biocompatible, has a low Tg, low vapor pressure and willdissolve, at or below 65° C., between about 30 weight % to about 60weight % crosslinkable prepolymer based upon the total weight of theviscous solution.
 90. The viscous solution of claim 89 wherein saiddiluents are selected from the group consisting of polyethylene glycols,glycerol, propylene glycol, dipropylene glycol and mixtures thereof. 91.The viscous solution of claim 90 wherein said diluents comprisepolyethylene glycols have molecular weights between about 200 and 600.92. The viscous solution of claim 88 wherein said diluent is polar andcomprises a boiling point less than about 150° C.
 93. The viscoussolution of claim 92 wherein said diluents are selected from the groupconsisting of alcohols, ether alcohols and mixtures thereof.
 94. Theviscous solution of claim 92 wherein said diluents are selected from thegroup consisting of 3 methoxy-1-butanone, methyl lactate,1-methoxy-2-propanol, 3-ethoxy-2-propanol, ethyl lactate, isopropyllactate and mixtures thereof.
 95. The viscous solution of claim 88further comprises at least one initiator.
 96. The viscous solution ofclaim 95 wherein said initiator comprises at least one photoinitiator,thermally activated initiator and mixtures thereof.
 97. The viscoussolution of claim 96 wherein said initiator is selected from the groupconsisting of bis(2,6-dimethoxybenzoyl)-2,4,4-trimethylpentyl phosphineoxide and diketone, 1-hydroxycyclohexylphenyl ketone.
 98. The viscoussolution of claim 88 further comprising a relaxation time of less thanabout 10 seconds.
 99. The viscous solution of claim 88 furthercomprising a relaxation time of less than about 5 seconds.
 100. Theviscous solution of claim 88 further comprising a relaxation time ofless than about 1 second.
 101. The composition of claim 75 where saidcrosslinkable prepolymer comprises a bimodal molecular weightdistribution.
 102. A hydrogel comprising a poly-HEMA network formed fromthe composition of claim
 75. 103. The hydrogel of claim 102 wherein saidhydrogel has a modulus of at least about 20 psi.
 104. The hydrogel ofclaim 102 wherein said modulus is between about 20 and about 90 psi.105. The hydrogel of claim 102 wherein said hydrogel has an elongationat break of greater than about 100%.
 106. The hydrogel of claim 102wherein said hydrogel has an elongation at break of greater than about120%.
 107. An article comprising the hydrogel of claim
 102. 108. Thearticle of claim 107 wherein said article comprises biomedical device.109. The article of claim 107 wherein said article is an ophthalmicdevice.
 110. The article of claim 109 wherein said ophthalmic device isa soft contact lens.
 111. An article comprising a polymer network formedfrom the composition of claim
 75. 112. A process comprising (a) shapingan article forming amount of viscous solution into an article form; and(b) curing said article form under conditions sufficient to form apolymer network.
 113. The process of claim 112 further comprising thestep of allowing said shaped form to relax before curing for a timesufficient to eliminate stresses induced by shaping.
 114. The process ofclaim 112 further comprising the step of allowing said shaped viscoussolution to rest prior to curing.
 115. The process of claim 114 whereinsaid shaped form is allowed to rest for a period which is about two toabout three times relaxation time for said viscous solution.
 116. Theprocess of claim 115 wherein said period is less than about 30 seconds.117. The process of claim 115 wherein said period is less than about 10seconds.
 118. The process of claim 115 wherein said period is less thanabout 5 seconds.
 118. The process of claim 112 wherein said viscoussolution, in formation of said article displays a shrinkage of less thanabout 2%.
 119. The process of claim 112 wherein said viscous solution,in the formation of said article displays a shrinkage of less than about1%.
 120. The process of claim 112 wherein said article comprisesbiomedical device.
 121. The process of claim 112 wherein said shaping isconducted via direct molding and said article is an ophthalmic device.122. The process of claim 112 wherein said ophthalmic device is a softcontact lens.
 123. The composition of claim 9 wherein at least onecomonomer is a tinted monomer that absorbs light in the visible and/orultraviolet range.
 124. The process of claim 56 wherein said diluentfurther comprises water.
 125. A composition comprising poly-HEMA havingless than about 10% polymer molecules having a peak molecular weight ofless than about 15,000.